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The pretreatment effect of chemical skin penetration enhancers in transdermal drug delivery using iontophoresis

 Choi EH  ;  Lee SH  ;  Ahn SK  ;  Hwang SM 
 Skin pharmacology and applied skin physiology, Vol.12(6) : 326-335, 1999 
Journal Title
 Skin pharmacology and applied skin physiology 
Issue Date
Administration, Cutaneous ; Animals ; Blood Glucose/metabolism ; Excipients/pharmacology* ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/pharmacokinetics ; Insulin/administration & dosage ; Insulin/pharmacokinetics ; Iontophoresis ; Mice ; Mice, Hairless ; Microscopy, Electron ; Pharmaceutical Preparations/administration & dosage* ; Rabbits ; Skin/drug effects ; Skin/ultrastructure ; Skin Absorption/drug effects* ; Stimulation, Chemical
The transdermal drug delivery (TDD) system has largely been divided into physical, biochemical and chemical methods. Recently, combinations of these methods were introduced for more effective delivery with less side effects. We performed this study to identify the effectiveness and mechanism of TDD using the physical method, 'iontophoresis', plus the chemical method, 'pretreatment with chemical enhancer'. The action sites of chemical enhancers in the stratum corneum (SC) were observed by electron microscope. We also studied whether this combined method synergistically impaired the skin barrier. To confirm the synergistic effect on skin penetration by this combined method, we measured the blood glucose level after insulin iontophoresis following a chemical enhancer pretreatment in rabbits. The results were that (1) dilatation of the intercellular lipid layers of the SC and lacunae was prominent in pretreatment with chemical enhancers inducing high transepidermal water loss (TEWL); (2) the skin barrier impairment, with repeated treatments showing an increased TEWL and also epidermal proliferation, was increased with the chemical enhancers that showed a high TEWL immediately after treatment; (3) the combination of chemical enhancer pretreatment and iontophoresis showed no synergistic impairment of the skin barrier, and (4) the chemical enhancer pretreatment with greater impairment of the skin barrier could increase the delivery of insulin by iontophoresis. The results showed that a combination of chemical enhancer pretreatment and iontophoresis could deliver drugs more effectively than iontophoresis alone. Our proposed theory is that iontophoretic drug delivery may be easier through the dilated intercellular spaces of the SC which have a lower electrical impedance following the chemical enhancer pretreatment. Because the effect and the side effects in the combination are decided by the chemical enhancer rather than iontophoresis, the development of proper chemical enhancers is important in future plans.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Seung Hun(이승헌)
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